A Novel Blood Test for the Early Detection of Alzheimer's Disease

Article type: Research Article

Authors: Rye, Phil. D.^{a; 1; 2} | Booij, Birgitte Boonstra^{a; 1; 3} | Grave, Gisle^a | Lindahl, Torbjørn^a | Kristiansen, Lena^a | Andersen, Hilde-Marie^a | Horndalsveen, Peter O.^b | Nygaard, Harald A.^{c; d} | Naik, Mala^{d; e} | Hoprekstad, Dagne^f | Wetterberg, Peter^g | Nilsson, Christer^h | Aarsland, Dagⁱ | Sharma, Praveen^a | Lönneborg, Anders^{a; *}

Affiliations: [a] DiaGenic ASA, Oslo, Norway | [b] Memory Clinic, Sanderud Hospital, Ottestad, Norway | [c] NKS Olaviken Hospital for Old Age Psychiatry, Erdal, Norway | [d] Section for Geriatric Medicine, Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway | [e] Geriatric Section, Haraldsplass Deaconess Hospital, Bergen, Norway | [f] Geriatric Clinic, Stavanger University Hospital, Stavanger, Norway | [g] Medical Division, Department of Geriatrics, Memory Clinic, Ullevål University Hospital, Oslo, Norway | [h] Department of Clinical Sciences, Lund University Hospital, Lund, Sweden | [i] Department of Psychiatry, Division of Mental Health Services, and Institute of Clinical Medicine, Stavanger University Hospital, and Akershus University Hospital, University of Oslo, Lørenskog, Norway

Correspondence: [*] Correspondence to: Dr. A. Lönneborg, DiaGenic ASA, Grenseveien 92, 0663 Oslo, Norway. Email: anders.lonneborg@diagenic.com.

Note: [1] Authors contributed equally to the manuscript.

Note: [2] Present address: Phil. D. Rye, GE Healthcare Medical Diagnostics, Nycoveien 2, P.O. Box 4220, Nydalen, 0401 Oslo, Norway.

Note: [3] Present address: Birgitte Boonstra Booij, Clavis Pharma, Parkveien 53 B, 0256 Oslo, Norway.

Abstract: Despite a variety of testing approaches, it is often difficult to make an accurate diagnosis of Alzheimer's disease (AD), especially at an early stage of the disease. Diagnosis is based on clinical criteria as well as exclusion of other causes of dementia but a definitive diagnosis can only be made at autopsy. We have investigated the diagnostic value of a 96-gene expression array for detection of early AD. Gene expression analysis was performed on blood RNA from a cohort of 203 probable AD and 209 cognitively healthy age matched controls. A disease classification algorithm was developed on samples from 208 individuals (AD = 103; controls = 105) and was validated in two steps using an independent initial test set (n = 74; AD = 32; controls = 42) and another second test set (n = 130; AD = 68; controls = 62). In the initial analysis, diagnostic accuracy was 71.6 ± 10.3%, with sensitivity 71.9 ± 15.6% and specificity 71.4 ± 13.7%. Essentially the same level of agreement was achieved in the two independent test sets. High agreement (24/30; 80%) between algorithm prediction and subjects with available cerebrospinal fluid biomarker was found. Assuming a clinical accuracy of 80%, calculations indicate that the agreement with underlying true pathology is in the range 85%-90%. These findings suggest that the gene expression blood test can aid in the diagnosis of mild to moderate AD, but further studies are needed to confirm these findings.

Keywords: Alzheimer's disease, biomarker, blood, diagnostic test, gene expression, RNA

DOI: 10.3233/JAD-2010-101521

Journal: Journal of Alzheimer's Disease, vol. 23, no. 1, pp. 121-129, 2011